An Exploratory Study of Epigenetic Age in Preeclamptic and Normotensive Pregnancy Reveals Differences by Self-Reported Race but Not Pregnancy Outcome.

Abstract

Preeclampsia is a leading cause of maternal and neonatal morbidity and mortality. Chronological age and race are associated with preeclampsia, but the role of these factors is not entirely understood. We hypothesized that DNA methylation age, a measure of biological age, would be higher in individuals with preeclampsia than in individuals with normotensive pregnancy and that DNA methylation age would differ by race across pregnancy. This was a longitudinal, exploratory study of 56 pregnant individuals (n = 28 preeclampsia cases and n = 28 normotensive controls). Genome-wide DNA methylation data were generated from trimester-specific peripheral blood samples. DNA methylation age was estimated using the "Improved Precision" clock, and ∆age, the difference between DNA methylation age and chronological age, was computed. DNA methylation age was compared with chronological age using Pearson correlations. The relationships between ∆age and preeclampsia status, self-reported race, and covariates were tested using multiple linear regression and performed both with and without consideration of cell-type heterogeneity. We observed strong correlation between chronological age and DNA methylation age across pregnancy, with significantly stronger correlation observed in White participants than in Black participants. We observed no association between ∆age and preeclampsia status. However, ∆age was higher in participants with higher pre-pregnancy body mass index in trimester 1 and lower in Black participants than in White participants in trimesters 2 and 3. Observations were largely consistent when controlling for cell-type heterogeneity. Our findings in a small sample support the need for additional studies to investigate the relationship between race and biological age, which could provide further insight into racial disparities across pregnancy. However, this study does not support an association between ∆age and preeclampsia status.